This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is to develop a multidisciplinary Center for the Analysis of Cellular Mechanisms and Systems Biology, to provide new infrastructure to advance understanding of cellular mechanisms, to better understand how to overcome disease, and to build a critical mass of faculty in this area. The Center is unique in Montana and the five surrounding states, and will include a combination of capabilities for analysis of cellular mechanisms. This project will create a powerful Mass Spectrometry and Proteomics Core infrastructure, oriented toward training researchers. Most cellular mechanisms appear to be controlled by protein post-translational modifications and the MS and Proteomics Core will add new mass spectrometers for improved characterization of modifications of proteins, high sensitivity microfluidic nano LC/MS/MS, a Hyperspectral imager for enhanced multicolor proteomic multiplexing to pin-point proteins that change with biological stimulation, and a protein electro-elution and microfluidic digestion system for high efficiency recovery of pin-pointed proteins. Sensitive differential protein detection capabilities developed at MSU and high sensitivity microfluidic nano LC/MS/MS will be included in the Core. New software will integrate data from an existing DNA microarray Facility. A Proteomics Reagent Synthesis Core will prepare new fluorescent reagents for differential analysis of changes in enzyme activity and post-translational modifications that result from biological stimulation. Critical mass will be built by supporting the development of three junior faculty and one senior faculty member, who is charting a new course in his research. Outstanding local and national mentors and External Advisory Committee members will guide the development of these faculty and the Center. Over the period of the project we plan to hire four new faculty in areas needed to build critical mass: a Chemical Biologist/Organic Synthesis expert, a Biological Mass Spectroscopist using advanced MS tools, a Systems Biologist working on metabolic modeling and metabolomics, and a Cell Biologist using global molecular tools. Outstanding MSU Institutional Support, the significance and timeliness of the post-genomic analysis of cellular mechanisms, and the orientation toward training in advanced methods will seed new projects-and will result in significant scientific contributions and a sustainable Center.